BACKGROUND & AIMS: The effectiveness of hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin is usually evaluated by the surrogate endpoint of sustained virologic response (SVR), although the ultimate goal of antiviral treatment is to reduce mortality. The impact of SVR on all-cause mortality is not well documented by HCV genotype or in populations in routine medical practice with substantial co-morbidities.

METHODS: From the United States Department of Veterans Affairs (VA), we identified all patients infected with HCV of genotypes 1, 2, or 3, without HIV co-infection or hepatocellular carcinoma prior to HCV treatment with pegylated interferon and ribavirin, who started HCV treatment from January 2001 to June 2007, stopped treatment by June 2008, and had a post-treatment HCV RNA test result of SVR or no SVR. Mortality data from VA and non-VA sources were available through 2009.

RESULTS: HCV genotype-1, -2, or -3 cohorts consisted of 12166, 2904, and1794 patients, respectively, with SVR rates of 35%, 72%, and 62%. Each cohort had high rates of co-morbidities. During a median follow-up of approximately 3.8 years, 1119 genotype-1, 220 gentoype-2, and 196 genotype-3 patients died. In genotype-specific multivariate survival models that controlled for demographic factors, co-morbidities, laboratory characteristics, and treatment characteristics, a SVR was associated with substantially reduced mortality risk for each genotype (genotype-1 hazard ratio [HR]=.70, P
CONCLUSION: A SVR reduced mortality among patients infected with HCV of genotypes 1, 2, or 3 who were being treated by routine medical practice and had substantial co-morbidities.